PROJECT SUMMARY As the breast cancer survivor population is growing significantly due to earlier diagnosis and extraordinary advancements in breast cancer treatment, these impressive outcomes in survival often come with a markedly decreased quality of life in survivorship. Pain and pain-related disability are one of the key negative consequences of surviving cancer reported in women treated for breast cancer, affecting 25 ? 80% of the survivorship population. Striking racial/ethnic health disparities are well established: African-American breast cancer survivors experience a disproportionate burden of pain compared to non-Hispanic Whites. The long- term goal of this project is to identify racial group differences in the pathophysiological mechanisms and psychosocial factors contributing to chronic pain in breast cancer survivors, and to use this knowledge (a) to determine unique variables which are of greatest importance for determining which patients are at risk for developing chronic pain and (b) to develop mechanism-based effective individualized interventions for pain relief and pain prevention in racially diverse breast cancer survivor populations. We hypothesize that racial group differences in pain and pain-related disability in breast cancer survivors will be mediated by differences in pain processing mechanisms, modulated by autonomic, psychosocial, and inflammatory parameters. To determine the effect of race on chronic pain in women treated for breast cancer we propose a longitudinal study of African-American and non-Hispanic White women diagnosed with stage I-IIIB breast cancer, who will be enrolled one year after completion of primary breast cancer treatment and assessed prospectively for a period of 18 months. Aim 1 will determine prospectively the prevalence, severity and time course of pain in African- American and non-Hispanic White breast cancer survivors. Aim 2 will characterize racial group differences in experimental pain sensitivity and pain modulatory parameters prospectively in African-American and non- Hispanic White breast cancer survivors using psychophysical measures. Aim 3 will determine the influence of race on the association between autonomic function and pain prospectively in African-American and non- Hispanic White breast cancer survivors. Aim 4 will assess the effect of race on the association between psychosocial processes and pain prospectively in African-American and non-Hispanic White breast cancer survivors. Aim 5 will assess the relationships between cytokines/chemokines, T-cell profiles and pain prospectively in African-American and non-Hispanic White women breast cancer survivors. The results of these studies are expected to have a major impact on racial pain disparities in breast cancer survivors by providing pathways for a personalized medicine approach based on the bio-psycho-social mechanisms involved that will allow to tailor treatment to the individual characteristics of each survivor, who is at risk to develop persistent pain. These studies will provide a key database of critical targets to design future clinical trials for the prevention and treatment of pain in racially diverse breast cancer survivors.